Molecular Transducers of Physical Activity Consortium

The goal of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) is to assess molecular changes that occur in response to physical activity (PA). To achieve this aim, a mechanistic randomized controlled trial (RCT) is conducted, in which adult study participants are randomized to endurance exercise (EE) training, resistance exercise (RE) training, or no exercise Control for a period of approximately 12 weeks. The overarching hypothesis is that there are discoverable molecular transducers that communicate and coordinate the effects of exercise on cells, tissues, and organs, which may initiate processes ultimately leading to the health benefits of exercise. Because this is a mechanistic trial, the main goal is not a single health-related outcome. Rather, the goal is to generate a resource leading to the generation of a map of the molecular responses to exercise that will be used by the Consortium and by the scientific community at large to generate hypotheses for future investigations of the health benefits of PA.

ADULT PARTICIPANT INCLUSION CRITERIA - SEDENTARY PARTICIPANTS * Willingness to provide informed consent to participate in the MoTrPAC Study * Must be able to read and speak English well enough to provide informed consent and understand instructions * Aged ≥18 y * Body Mass Index (BMI) ≥19 to ≤35 kg/m2 * Sedentary defined as self-reporting no more than 1 day per week, lasting no more than 60 minutes, of regular (structured) EE \[e.g., brisk walking, jogging, running, cycling, elliptical, or swimming activity that results in feelings of increased heart rate, rapid breathing, and/or sweating\] or RE (resulting in muscular fatigue) in the past year * Persons bicycling as a mode of transportation to and from work \>1 day/week etc. are not considered sedentary * Leisure walkers are included unless they meet the heart rate, breathing, and sweating criteria noted above * Willingness to include de-identified individual-level data at low risk of re-identification (e.g.,non-genomic data) in the MoTrPAC open-access database * Only one member of a household can participate ADULT PARTICIPANT INCLUSION CRITERIA - HIGHLY ACTIVE PARTICIPANTS * Willingness to provide informed consent to participate in the MoTrPAC Study * Must be able to read and speak English well enough to provide informed consent and understand instructions * Aged ≥18 y * BMI ≥19 to ≤35 kg/m2 * Comparator Participants * HAEE: defined as ≥240 minutes/week of ET for ≥1 year; this can include running, walking (brisk, power), cycling, elliptical, etc. which (at a minimum) results in increased heart rate, rapid breathing and sweating * Must include cycling at least 2 days/week * RT in the past year must be limited to ≤2 days/week of upper body RE and ≤2 muscle groups of upper body RE and ≤1 day/week of lower body RE * HARE: defined as RT of ≥3 upper and ≥3 lower body muscle groups ≥2 times/week for ≥1 year; using a prescription sufficient to increase strength and muscle mass * ET in the past year must be limited to ≤90 minutes/week of vigorous EE, with no limit on cycling days per week * Elite or Competitive Athletes: can be included, if they meet HAEE or HARE inclusion criteria * Potential participants are informed that use of performance enhancing drugs in the last 6 months is exclusionary * Willingness to include de-identified individual-level data at low risk of re-identification (e.g., non-genomic data) in the MoTrPAC open-access database * In addition to meeting HAEE or HARE inclusion criteria, all HA participants must meet all other exclusion criteria defined in this protocol EXCLUSION CRITERIA ADULT PARTICIPANT EXCLUSION CRITERIA Exclusion criteria are confirmed by self-report (i.e., medical and medication histories reviewed by a clinician), screening tests performed by the MoTrPAC study team at each clinical site, and/or clinician judgement as specified for each criterion. * Diabetes (self-report and screening tests) * Treatment with any hypoglycemic agents (self-report) or A1c \>6.4% (screening test; may reassess once if 6.5-6.7%) * Fasting glucose \>125 mg/dL (screening test; may reassess once) * Use of hypoglycemic drugs for non-diabetic reasons (self-report) * Abnormal bleeding or coagulopathy (self-report) * History of a bleeding disorder or clotting abnormality * Thyroid disease (screening test) * Thyroid Stimulating Hormone (TSH) value \>5.9 IU/mL * Individuals with hypothyroidism may be referred to their primary care provider (PCP) for evaluation and retested; any medication change must be stable for ≥3 months prior to retesting * Individuals with hyperthyroidism are excluded, including those with normal TSH on pharmacologic treatment * Pulmonary (self-report) * Clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD) * Metabolic bone disease (self-report) * History of non-traumatic fracture from a standing height or less * Current pharmacologic treatment for low bone mass or osteoporosis, other than calcium, vitamin D, or estrogen * Estrogens, progestins (self-report) * Supplemental, replacement or therapeutic use of estrogens or progestins within the last 6 months, other than birth control or to control menopausal symptoms * Pregnancy (screening test) and pregnancy-related conditions (self-report) * Pregnant - pregnancy test performed on day of DXA scan in women of child-bearing potential * Post-partum during the last 12 months * Lactating during the last 12 months * Planning to become pregnant during the participation period * Elevated blood pressure readings (screening test) * Resting Systolic Blood Pressure (SBP) ≥150 mmHg or Resting Diastolic Blood Pressure (DBP) ≥95 mmHg * Reassessment of BP during screening will be allowed to ensure rested values are repeatable * Cardiovascular (self-report, screening test, and clinician judgement) * Congestive heart failure, coronary artery disease, significant valvular disease, congenital heart disease, serious arrhythmia, stroke, or symptomatic peripheral artery disease (self-report, screening test) * Specific criteria used to determine whether a volunteer can undergo the screening CPET follow the American Heart Association (AHA) Criteria \[54\] * Inability to complete the CPET * Reassessment of the CPET may be allowed under some circumstances (e.g., test was not a maximal effort) * Abnormal blood lipid profile (screening test) * Fasting triglycerides \>500 mg/dL * Low-density lipoprotein cholesterol (LDL-C) \>190mg/dL * Cancer (self-report) * History of cancer treatment (other than non-melanoma skin cancer) and not "cancer-free" for at least 2 years * Anti-hormonal therapy (e.g., for breast or prostate cancer) within the last 6 months * Chronic active or latent infection (self-report) * Active or latent infections requiring chronic antibiotic or anti-viral treatment * Chronic active infection whether on chronic antimicrobials or not * Human Immunodeficiency Virus * Active hepatitis B or C undergoing antiviral therapy * Individuals successfully treated for hepatitis C and virologically negative for at least 6 months are not excluded * Liver enzyme tests (Alanine transaminase, Aspartate transaminase) (screening test) * \>2 times the laboratory upper limit of normal * Reassessment during screening may be allowed under some conditions (e.g., recent use of acetaminophen) * Individuals may be referred to their PCP for evaluation; any medication change must be stable for ≥3 months prior to retesting * Chronic renal insufficiency (screening test) * Estimated glomerular filtration rate \3 points outside of the local normal laboratory ranges for women and men * Reassessment may be allowed under certain conditions * Individuals may be referred to their PCP for evaluation; any medication change must be stable for ≥3 months prior to retesting * Individuals with known thalassemia trait may be included (despite having \>3 points outside of the local normal laboratory ranges), upon approval from their PCP or a hematologist * Blood donation (self-report) * Whole blood donation in the last 3 months or plans for blood donation during the entire protocol period * Platelet or plasma donation in the last week or plans for platelet or plasma donation during the entire protocol period * Autoimmune disorders (self-report) * Individuals receiving any active treatment (including monoclonal antibodies) within the last 6 months * Alcohol consumption (self-report) * More than 7 drinks per week for women * More than 14 drinks per week for men * History of binge drinking (≥5 drinks for males or ≥4 drinks for females in a 2-hour period more than once per month) * Tobacco (self-report) * Current smokers: any tobacco or e-cigarette/e-nicotine products * Former smokers: * Stopped smoking \